HER-2 amplification

ESR1 alterations were most frequent in HR + /HER2- BC samples and missense mutations were more frequent in metastatic samples, consistent with their role in ET resistance and disease progression. ESR1 alterations co-occurred with therapeutically relevant alterations in other genes that may help inform clinical decision-making. Gynecologic tumors harbored ESR1 alterations that have prognostic and potentially therapeutic relevance.

Using this tool to mimic the mutation-specific dynamics in MCF10A mammary epithelial cells, we found that PI3K signaling patterns alone were sufficient to reproduce key features of the PIK3CA H1047R-associated EMT phenotype but not the ErbB2-associated proliferative phenotype. These findings suggest that the temporal encoding of pathway activity, not merely its magnitude, can drive some phenotypic changes in oncogenic progression, explain how distinct mutations within a common signaling pathway can produce divergent cellular phenotypes, and provide a workflow for interrogating the functional consequences of changes in signaling dynamics.

Moreover, BB-1701, a novel HER2-ADC containing eribulin as a payload, to which N87 AR cells are sensitive, exhibited antitumor effects in N87 AR cells in vitro and in vivo. These findings indicate that ABC transporter-mediated drug efflux is an important mechanism underlying T-DXd resistance in HER2-positive gastric and lung cancer models. Furthermore, our study suggests that both targeting drug efflux pathways and utilizing alternative payloads may be effective strategies for overcoming T-DXd resistance in HER2-positive gastric and lung cancers.

Postoperatively, the patient was started on tamoxifen, and she remains recurrence-free to date. This case underscoring the importance of careful pre-treatment assessment of malignancy.

P2, N=47, Active, not recruiting, Dana-Farber Cancer Institute | Trial completion date: Nov 2025 --> May 2026

P=N/A, N=7933, Not yet recruiting, Boehringer Ingelheim

Molecular testing has become an essential component of modern iCCA management. Broad, early, and technically integrated molecular profiling-ideally performed at initial diagnosis and interpreted in an interdisciplinary (molecular) tumor board-is critical to fully realize the potential of precision oncology in BTC.

The integration of additional biomarker assessments into MTB workflows enhances precision oncology by expanding the pool of patients eligible for targeted therapies.

P1, N=93, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Oct 2025 --> Oct 2028 | Trial primary completion date: Oct 2025 --> Oct 2028

This study provides a comprehensive molecular profiling of BTCs in the Indian population, revealing key genomic alterations, subtype-specific differences, and associations with immune features. The findings underscore the importance of molecular profiling in guiding personalized treatment strategies.

Emerging single-cell and spatial transcriptomic analyses have further refined this landscape by deconstructing tumor microenvironments and potential evolutionary trajectories associated with disease progression. This review examines the evolution of molecular classification systems for gastric cancer, highlights current consensus frameworks, and discusses how subtype-based stratification will transform clinical trial design and enable biomarker-driven precision therapy.

P2, N=30, Recruiting, M.D. Anderson Cancer Center | Trial completion date: Dec 2026 --> Jul 2028 | Trial primary completion date: Dec 2025 --> Jul 2028